DESCRIPTION: (Applicant s abstract) Because of the greater life expectancy of today, menopause and its physiological consequences are having an enormous impact on the well-being of the older female. The present research is concerned with identifying, elucidating, and quantifying the ovarian and neuroendocrine mechanisms underlying menopause. In particular, to establish that there is a specific sequential pattern of five phases that occurs during the menopausal transition, and to construct statistical predictors of the onset age and duration of the menopausal transition. Moreover, such a predictor will also allow for the estimation of a given subject's hormonal- reproductive age, not chronological age, which has enormous implications for the infertility consequences of aging. For example, based upon certain endocrine reproductive measurements taken from say a given 40 year-old female, methods will be constructed by which to predict her age of perimenopause onset and its length, and at same time to state whether she is hormonally that of a 40 year-old, or more like a 45 or 35 year-old. The ability to predict the age and length of the menopausal transition is clinically important because early menopause has associated with it increased risk of cardiovascular disease and osteoporosis, whereas late menopause has associated with it an increased risk of breast cancer and endometrial cancer. This research consists of three components. First, five prospective and cross-sectional clinical studies specifically designed for the above aims will be conducted at the University of Virginia GCRC, using pre-, peri-, and postmenopausal subjects. Second, a biomathematical model for the aging hypothalamic-pituitary- ovarian axis will be developed which includes its several feedback/feed forward interactions, the dynamical onset and shutdown of the LH surge and ovulation, as well as its eventual cessation. Third, based upon the preceding two, hypotheses concerning the five phases will be tested, and predictors of onset age and duration constructed.